MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells

Chronic lymphocytic leukemia (CLL) is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA) expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from no...

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Bibliographic Details
Published in:PloS one 2011-03, Vol.6 (3), p.e16956-e16956
Main Authors: Li, Shuqiang, Moffett, Howell F, Lu, Jun, Werner, Lillian, Zhang, Hao, Ritz, Jerome, Neuberg, Donna, Wucherpfennig, Kai W, Brown, Jennifer R, Novina, Carl D
Format: Article
Language:English
Subjects:
Adenosine
Analysis
Apoptosis
B cells
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Biology
Cancer
Cell activation
Cell growth
Chronic lymphocytic leukemia
Cloning
Defects
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Gene set enrichment analysis
Genes
Humans
Immunology
Kinases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - therapy
Lymphatic leukemia
Lymphocyte Activation - genetics
Lymphocyte receptors
Lymphocytes
Lymphocytes B
Lymphoma
Medical schools
Medicine
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Pathogenesis
Phenotype
Reproducibility of Results
Ribonucleic acid
RNA
Statistical analysis
Time Factors
Transgenic animals
Tumors
ZAP-70 protein
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Summary:Chronic lymphocytic leukemia (CLL) is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA) expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA) identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70(+) and IgV(H) unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0016956